Identification of an ATP/P2X7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness

Authors

Xiaomei Kong
William C Bennett
Corey M Jania
Kelly D Chason
Zachary German
Jennifer Adouli
Samuel D Budney
Brandon T Oby
Catharina van Heusden
Eduardo R Lazarowski
Ilona Jaspers
Scott H Randell
Barry A Hedgespeth
Glenn Cruse
Xiaoyang Hua
Stephen A Schworer
Gregory J Smith
Samir Np Kelada
Stephen L Tilley

Publication Date

11-8-2021

Journal

JCI Insight

Abstract

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR.

Keywords

Adenosine Triphosphate, Animals, Bronchial Hyperreactivity, Female, Humans, Mast Cells, Mice, Ozone

Comments

Supplementary Materials

PMID: 34546976